Cyclic compounds, including polycyclic compounds, are useful as dyes, pesticides, pharmaceuticals, and in the electronics industry, inter alia. Currently there is a need for methods that can be used to prepare cyclic compounds. In particular, there is a need for methods that can be carried out under mild conditions. Such methods may be particularly useful for preparing complicated cyclic ring systems as well as cyclic ring systems that possess sensitive functionality that may be damaged by the conditions required by many cyclization methods. There is also a need for methods that can lead to highly substituted cyclic ring systems.
o-Benzyne (or 1,2-didehydrobenzene, 1, Scheme 1) is one of the oldest, most interesting, and most well studied of all reactive intermediates in chemistry. Methods for generating benzynes involve the removal of two adjacent atoms or substituents from precursors 2. The multifaceted and often highly efficient reactions of benzynes with suitable trapping reagents (cf. 1 to 3) have long been exploited, often in the service of synthetic organic chemistry. Even by 1967 myriad such reactions, recorded in a substantial monograph, were known (see Hoffmann, R. W. Organic Chemistry, A Series of Monographs—Volume 11, Academic Press, New York, 1967). Nonetheless, newly discovered benzyne reaction motifs continue to emerge; this Renaissance attests to yet additional versatility of this remarkable intermediate. Nearly all benzyne trapping reactions (regardless of whether occurring via a stepwise or an asynchronous/polarized concerted mechanistic pathway) are initiated by in-plane nucleophilic attack by electron density in the trapping agent (Nu-El) on the highly strained alkyne in 1.

The Diels-Alder [4+2] cycloaddition reaction (Scheme 2) is, arguably, the most venerable/revered reaction in all of chemistry. The prototypical event involves addition of a 1,3-diene 4π-component (5) with an alkenyl dienophile 4 and results in a cyclohexene product 6 at the oxidation state of a tetrahydrobenzene. If an alkyne is used as the dienophile (7), a 1,4-cyclohexadiene (or 1,4-dihydrobenzene, 8 results); this can be viewed as a didehydro-Diels-Alder reaction. Another well-known variant involves engagement of a (yet more highly oxidized) 1,3-enyne (9) as the 4π-component with an alkyne (7). This produces a transient cyclic allene 10 that rapidly rearranges via a [1,5]-hydrogen atom shift to produce (the yet more highly oxidized) benzene (11).

The most highly oxidized Diels-Alder variant is the cycloaddition between a 1,3-diyne 12 and an alkynyl diynophile (7), which generates o-benzyne directly. Given the potential generality of this reaction, it is surprising that it has not been highly exploited. However, 4+2 cyclizations leading to benzynes have received only limited attention. See for example, K. Miyawaki, et al., Tetrahedron Lett., 1997, 38, 3943-3946; A. Bradley and R. Johnson, J. Am. Chem. Soc., 1997, 119, 9917-9918; K. Miyawaki, et al., Tetrahedron Lett., 1998, 39, 6923-6926; I. Ueda, et al., Tetrahedron Lett., 1999, 40, 319-322; I. Ueda, et al., Tetrahedron Lett., 2000, 41, 1447-1451; K. Miyawaki, et al., Heterocycles., 2000, 54, 887-900; T. Kawano, et al., Tetrahedron Lett., 2005, 46, 1233-1236; T. Kawano, et al., Bull. Chem. Soc, Jpn., 2006, 79, 944-949; K. Torikai, et al., Bioorganic and Medicinal Chemistry, 2008, 16, 5441-5451; J. Tsui and B. Sterenberg, Organometallics, 2009, 28, 4906-4908; R. Johnson, J. Phys. Org. Chem., 2010, 23, 283-292; T. Kitamura, Aust. J. Chem., 2010, 63, 987-1001; and K. Cahill, et al., Aust. J. Chem., 2010, 63, 1007-1012.